Bone Marrow Harvest: A White Paper of Best Practices by the NMDP Marrow Alliance.

Data on recent bone marrow harvest collections from the NMDP has shown that bone marrow quality has decreased based on total nucleated cell count in the product. To ensure that quality bone marrow products are available to all recipients, the NMDP Marrow Alliance was formed in April of 2021 to increase the ability for bone marrow collection centers to safely deliver high-quality products consistently and to identify and disseminate guidelines for performing bone marrow harvests. This White Paper describes the best practices of performing a bone marrow harvest as defined by the NMDP Marrow Alliance.

An International Learning Collaborative Phase 2 Trial for Haploidentical Bone Marrow Transplant in Sickle Cell Disease.

In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that non-myeloablative related haploidentical BMT with thiotepa and post-transplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants (median age 19.1 (IQR 14.1 - 25.0) were evaluable based on the conditioning protocol. Graft failure occurred in 11.4% (8/70) and only in participants <18 years (p=0.001); all had autologous reconstitution. After a median follow-up of 2.4 years (IQR 1.5-3.9), the 2-year Kaplan-Meier-based probability of event-free survival was 82.6% (95% CI 71.4%-89.7%). The 2-year overall survival was 94.1% (95% CI 84.9%-97.7%) with no difference between the child and adult participants (p=0.889). After excluding participants with graft failure (n=8), participants with engraftment had median whole blood donor chimerism values at D+180 and D+365 post-transplant of 100.0% (IQR 99.8 - 100.0%; n=59) and 100.0% (IQR 100.0 - 100.0%; n=58), respectively, and 96.6% (57/59) were off immunosuppression at 1-year post-transplant. The 1-year grades III-IV acute graft versus host disease (GvHD) rate was 10.0% (95% CI 4.6 - 18.6%), and the 2-year moderate-severe chronic GvHD rate was 10.0% (95% CI 4.6 - 18.6%). Five participants (7.1%) died from infectious complications. We demonstrate that non-myeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, instead of the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates (ClinicalTrials.gov identifier NCT01850108).

Transcranial doppler velocity in iron-deficient Nigerian children with sickle cell anemia.

Oral iron supplementation in iron deficient children with sickle cell anemia and normal transcranial Doppler ultrasound (TCD) velocities does not reduce arterial flow in the middle cerebral artery.

Burden of employment loss and absenteeism in adults and caregivers of children with sickle cell disease.

ABSTRACT: Sickle cell disease (SCD) is a genetic disorder affecting 100 000 people with an estimated annual medical cost of $3 billion in the United States; however, the economic impact on patients is not well described. We aimed to examine the indirect economic burden and test the hypothesis that socioeconomic status and greater social vulnerability risks are associated with increased absenteeism and employment loss. We surveyed adults and caregivers of children with SCD at 5 US centers from 2014 to 2021. Logistic regression models were used to examine the associations of employment loss and missed days of work with demographics and social determinants. Indirect costs were estimated by multiplying the self-reported missed days of work and job loss by 2022 average wages by the state of the participating institution. Of the 244 participants, 10.3% reported employment loss in the last 5 years, and 17.5% reported missing 10 or more days of work. Adults had 3 times more employment loss compared with caregivers of children with SCD (OR, 3.18; 95% CI, 1.12-9.01) but fewer missed days of work (OR, 0.24; 95% CI, 0.11-0.0.51). Participants who did not live with a partner reported increased employment loss (OR, 4.70; 95% CI, 1.04-21.17) and more missed days of work (OR, 4.58; 95% CI, 1.04-20.15). The estimated annual indirect economic burden was $2 266 873 ($9290 per participant). Adults with SCD and caregivers of children with SCD commonly report employment loss and missed days of work as important risk factors. The high indirect economic burden suggests that future economic evaluations of SCD should include SCD-related indirect economic burden.

Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease.

ABSTRACT: Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.3 ± 8.9 years; 389 ± 150 days after HSCT) with age-, race- and sex-matched values from healthy adults without sickle trait (n = 28; age, 30.2 ± 5.6 years). Before transplant, 7 patients had neurological indications for transplant (eg, overt stroke) and 4 had nonneurological reasons for haploidentical bone marrow transplant (haplo-BMT). All received haplo-BMT from first-degree relatives (parent, sibling, or child donor) with reduced-intensity preparation and maintained engraftment. Before transplant, CBF was elevated (CBF, 69.11 ± 24.7 mL/100 g/min) compared with that of controls (P = .004). Mean CBF declined significantly after haplo-BMT (posttransplant CBF, 48.2 ± 13.9 mL/100 g/min; P = .003). OEF was not different from that of controls at baseline and did not change significantly after haplo-BMT (pretransplant, 43.1 ± 6.7%; posttransplant, 39.6 ± 7.0%; P = .34). After transplant, CBF and OEF were not significantly different from controls (CBF, 48.2 ± 13.4 mL/100 g/min; P = .78; and OEF, 39.6 ± 7.0%; P > .99). CMRO2 did not change significantly after haplo-BMT (pretransplant, 3.18 ± 0.87 mL O2/100 g/min; posttransplant, 2.95 ± 0.83; P = .56). Major complications of haplo-BMT included 1 infection-related death and 1 severe chronic graft-versus-host disease. Haplo-BMT in adults with SCD reduces CBF to that of control values and maintains OEF and CMRO2 on average at levels observed in healthy adult controls. The trial was registered at www.clinicaltrials.gov as #NCT01850108.

The range of haploidentical transplant protocols in sickle cell disease: all haplos are not created equally.

The ideal curative therapy for sickle cell disease (SCD) must be applicable across all ages and include individuals with strokes and preexisting heart, lung, and kidney disease. Myeloablative, matched sibling donor hematopoietic stem cell transplant (HCT) for children with SCD has shown excellent outcomes over the past 3 decades but has been restricted due to the limited availability of a human leukocyte antigen-matched sibling donor (10%-15%) and increased treatment-related death in adults with myeloablative conditioning. To overcome these 2 significant barriers to curative therapy in SCD, related haploidentical HCT has become an active area of research. The use of related haploidentical donors (first- and second-degree relatives) increases the donor pool to at least 90% of those eligible across the life span. Importantly, most adults, even with strokes or significant comorbidities, can tolerate the nonmyeloablative conditioning regimen without treatment-related death. Since 2013, at least 3 related haploidentical HCT strategies have emerged as potential curative therapies for SCD: (1) a nonmyeloablative, T-cell replete, bone marrow transplant with thiotepa and posttransplant cyclophosphamide with a goal of complete donor chimerism; (2) a nonmyeloablative, in vivo T-cell depletion, using peripheral blood stem cells (PBSCs) with a goal of stable mixed donor-recipient chimerism; and (3) a myeloablative, ex vivo T-cell depletion using PBSCs and advanced-technology graft manipulation, with a goal of complete donor chimerism. We review the similarities, differences, outcomes, and gaps in knowledge with these 3 haploidentical HCT approaches for SCD.

A feasibility randomized controlled trial of an mHealth app vs booklets for patient-facing guidelines in adults with SCD.

Despite the increased number of evidence-based guidelines for sickle cell disease (SCD), dissemination of evidence-based guidelines in lay language for individuals or families with SCD has not been evaluated. We conducted a feasibility randomized controlled trial to determine the acceptability of a mobile health (mHealth) app with patient-facing guidelines to improve the knowledge of individuals with SCD about SCD-specific knowledge and reduce hospitalizations. Primary outcome measures include recruitment, retention, and adherence rates. Adults with SCD were enrolled at 2 sickle cell centers between 2018 and 2022. Participants were randomized to receive either an mHealth app + booklet with patient-facing guidelines or a booklet with the guidelines alone. Participants completed surveys at baseline and a final 6-month visit. Approximately 67 of 74 (91%) agreed to participate and were randomized, with 50 of 67 (75%) completing all the study components. All participants who completed the study in the treatment arm used the app. Our results demonstrated high recruitment, retention, and adherence rate for the first randomized trial for an mHealth app with patient-facing guidelines in adults with SCD. This clinical trial was registered at https://www.clinicaltrials.gov/ as #NCT03629678.

Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume.

Introduction: Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and contemporary methods could motivate the use of longitudinal brain volume assessment in SCD as an automated marker of disease stability or future progression. The purpose of this study was to rigorously evaluate whether children and young adults with SCD have reduced gray matter volume (GMV) and white matter volume (WMV) compared to healthy controls using high-resolution MRI. We tested the hypotheses that (i) elevated CBF, a marker of cerebral hemodynamic compensation in SCD, is associated with global and regional brain atrophy, and (ii) silent cerebral infarct burden is associated with brain atrophy in excess of infarct volume. Methods: Healthy controls (n = 49) and SCD participants without overt stroke (n = 88) aged 7-32 years completed 3 T brain MRI; pseudocontinuous arterial spin labeling measured CBF. Multivariable linear regressions assessed associations of independent variables with GMV, WMV, and volumes of cortical/subcortical regions. Results: Reduced hemoglobin was associated with reductions in both GMV (p = 0.032) and WMV (p = 0.005); reduced arterial oxygen content (CaO2) was also associated with reductions in GMV (p = 0.035) and WMV (p = 0.006). Elevated gray matter CBF was associated with reduced WMV (p = 0.018). Infarct burden was associated with reductions in WMV 30-fold greater than the infarct volume itself (p = 0.005). Increased GM CBF correlated with volumetric reductions of the insula and left and right caudate nuclei (p = 0.017, 0.017, 0.036, respectively). Infarct burden was associated with reduced left and right nucleus accumbens, right thalamus, and anterior corpus callosum volumes (p = 0.002, 0.002, 0.009, 0.002, respectively). Discussion: We demonstrate that anemia and decreased CaO2 are associated with reductions in GMV and WMV in SCD. Increased CBF and infarct burden were also associated with reduced volume in subcortical structures. Global WMV deficits associated with infarct burden far exceed infarct volume itself. Hemodynamic compensation via increased cerebral blood flow in SCD seems inadequate to prevent brain volume loss. Our work highlights that silent cerebral infarcts are just a portion of the brain injury that occurs in SCD; brain volume is another potential biomarker of brain injury in SCD.

Relapsed or refractory large B-cell lymphoma after chimeric antigen receptor T-cell therapy: Current challenges and therapeutic options.

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy can provide durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after failure of chemoimmunotherapy. However, patients who are refractory or relapsing after CAR-T therapy have poor outcomes. Multiple mechanisms of CAR-T therapy failure have been proposed but management of these patients remains a challenge. As CAR-T therapy moves earlier in the treatment of DLBCL, we urgently need trials focused on patients with relapse after CAR-T therapy. Recent advances in novel immunotherapies such as bispecific antibodies, antibody-drug conjugates and next-generation CAR-T therapies may provide avenues for treatment. Here we review the available data on using these drugs after failure of CAR-T therapy and provide a framework for the ideal sequencing of these novel agents.

Creating an automated contemporaneous cohort in sickle cell anemia to predict survival after disease-modifying therapy.

The Food and Drug Administration requires contemporaneous controls to compare clinical outcomes for participants receiving experimental gene therapy or gene editing clinical trials. However, developing a contemporaneous cohort of rare diseases requires multiple person-hours. In a single referral center for sickle cell disease, we tested the hypothesis that we could create an automated contemporaneous cohort of children and adults with sickle cell anemia (SCA) to predict mortality. Data were obtained between 1 January 2004 and 30 April 2021. We identified 419 individuals with SCA with consistent medical care defined as followed continuously for >0.5 years with no visit gaps >3.0 years. The median age was 10.2 years (IQR, 1-24 years), with a median follow-up of 7.4 years (IQR, 3.6-13.5 years) and 47 deaths. A total of 98% (274 of 277) of the children remained alive at 18 years of age, and 34.3% (94 of 274) of those children were followed into adulthood. For adults, the median age of survival was 49.3 years. Treatment groups were mutually exclusive and in a hierarchical order: hematopoietic stem cell transplant (n = 22)>regular blood transfusion for at least 2 years (n = 56)>hydroxyurea for at least 1 year (n = 243)>no disease-modifying therapy (n = 98). Compared to those receiving no disease-modifying treatment, those treated with hydroxyurea therapy had a significantly lower hazard of mortality (hazard ratio = 0.38; P = 0.016), but no statistical difference for those receiving regular blood transfusions compared to no disease-modifying therapy (hazard ratio = 0.71; P = 0.440). An automated contemporaneous SCA cohort can be generated to estimate mortality in children and adults with SCA.

Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial.

We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval [CI], 0.32-3.00; P = .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18; 95% CI, 0.30-4.88; P = .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention.

Evaluation of healthcare-associated infection rates in patients with hematologic malignancies and stem cell transplantation during the coronavirus disease 2019 (COVID-19) pandemic.

Objective: To evaluate whether rates of healthcare-associated infections (HAIs) changed during the coronavirus disease 2019 (COVID-19) pandemic in malignant hematology and stem cell transplant patients. Design: A retrospective, cohort study. Patients: The study included malignant hematology and stem cell transplant patients admitted between March 1, 2019, through July 31, 2019, and March 1, 2020, through July 31, 2020. Methods: Rates of catheter-associated urinary tract infections (CAUTIs), central-line-associated bloodstream infections (CLABSIs), central-line-associated mucosal barrier injury infections (CLAMBIs), and Clostridioides difficile infections (CDIs) during the pandemic were compared to those in a control cohort. Secondary outcomes included the rate of non-COVID-19 respiratory viruses. Results: The rate of CAUTIs per 1,000 hospital days was 0.435 before the pandemic and 0.532 during the pandemic (incidence rate ratio [IRR], 1.224; 95% confidence interval [CI], 0.0314-47.72; P = .899). The rate of CLABSIs was 0.435 before the pandemic and 1.064 during the pandemic (IRR, 2.447; 95% CI, 0.186-72.18; P = .516). The rate of CLAMBIs was 2.61 before the pandemic and 1.064 during the pandemic (IRR 0.408, 95% CI 0.057-1.927; P = .284). The rate of CDIs was 2.61 before the pandemic and 1.579 during the pandemic (IRR, 0.612; 95% CI, 0.125-2.457; P = .512). Non-COVID-19 respiratory virus cases decreased significantly from 12 (30.8%) to 2 cases (8.3%) (P = 0.014). Conclusions: There was no significant difference in HAIs among inpatient malignant hematology and stem cell transplant patients during the COVID-19 pandemic compared to those of a control cohort. Rates of infection were low among both cohorts. Rates of community-acquired respiratory viruses decreased significantly during the pandemic among this population.

Debating the Future of Sickle Cell Disease Curative Therapy: Haploidentical Hematopoietic Stem Cell Transplantation vs. Gene Therapy.

Hematopoietic stem cell transplantation (HSCT) is a well-established curative therapy for patients with sickle cell disease (SCD) when using a human leukocyte antigen (HLA)-matched sibling donor. Most patients with SCD do not have a matched sibling donor, thereby significantly limiting the accessibility of this curative option to most patients. HLA-haploidentical HSCT with post-transplant cyclophosphamide expands the donor pool, with current approaches now demonstrating high overall survival, reduced toxicity, and an effective reduction in acute and chronic graft-vs.-host disease (GvHD). Alternatively, autologous genetic therapies appear promising and have the potential to overcome significant barriers associated with allogeneic HSCT, such as donor availability and GvHD. Here the authors each take a viewpoint and discuss what will be the future of curative options for patients with SCD outside of a matched sibling transplantation, specifically haploidentical HSCT vs. gene therapy.

SARS-CoV-2 vaccine safety and immunogenicity in patients with hematologic malignancies, transplantation, and cellular therapies.

Individuals with hematological malignancies and hematopoietic stem cell transplant (HCT) recipients are immunologically heterogenous groups with varying degrees of immunosuppression at increased risk of severe disease and mortality from SARS-CoV-2 infection. SARS-CoV-2 vaccines are key interventions to preventing severe COVID-19 and its complications. While these individuals were excluded from initial vaccine trials, there is now a growing body of acceptable safety and immunogenicity data among these individuals. A consistent signal for new or worsening graft versus host disease in allogeneic HCT recipients has not been demonstrated post-vaccination. Immunogenicity in these populations is variable depending on disease and treatment factors. However, serological responses may not accurately reflect vaccine protection as correlates of protection within these populations are not yet established. Large-scale studies powered to identify rare serious events, resolve differences in vaccine responses between different vaccination strategies, and identify immune correlates of protection within these populations are needed.

Reduction in seroprevalence of viral transfusion-transmitted infections in southwest Nigeria in children with sickle cell disease using an enhanced screening strategy.

Blood transfusion is an integral component in the management of children and adults with sickle cell disease (SCD). Concerns about blood safety due to the high risk of bloodborne infections in sub-Saharan Africa limits the application of this cost-effective strategy in the management of individuals with SCD. In a single-centre, retrospective, longitudinal study in southwest Nigeria, we hypothesised that the use of stringent blood donor selection, along with very sensitive enzyme-linked immunosorbent assay (ELISA) screening methods would reduce transfusion-transmitted infections (TTIs). Among 45 002 eligible blood donors at the Lagos University Teaching Hospital in Nigeria, over a 5-year review period (2015-2019), the seroprevalence rate of viral TTIs was 9.83%. The seroprevalence rates for human immunodeficiency, hepatitis B, and hepatitis C viruses were 1.37%, 6.2%, and 2.25% respectively. Among 172 children with SCD, 71% (122/172) on regular blood transfusion and 29% (50/172) who had never been transfused or had less than two transfusions per lifetime, none acquired any TTIs using our enhanced screening approach during the study period. Thus, safe blood transfusion practices can be provided for children with SCD in sub-Saharan Africa with the use of stringent donor selection protocols and fourth-generation ELISA kits for TTI screening.

Characterizing Intracranial Hemodynamics in Sickle Cell Anemia: Impact of Patient-Specific Viscosity.

PURPOSE: Pediatric and adult patients with sickle cell anemia (SCA) are at increased risk of stroke and cerebrovascular accident. In the general adult population, there is a relationship between arterial hemodynamics and pathology; however, this relationship in SCA patients remains to be elucidated. The aim of this work was to characterize circle of Willis hemodynamics in patients with SCA and quantify the impact of viscosity choice on pathophysiologically-relevant hemodynamics measures. METHODS: Based on measured vascular geometries, time-varying flow rates, and blood parameters, detailed patient-specific simulations of the circle of Willis were conducted for SCA patients (n = 6). Simulations quantified the impact of patient-specific and standard blood viscosities on wall shear stress (WSS). RESULTS: These results demonstrated that use of a standard blood viscosity introduces large errors into the estimation of pathophysiologically-relevant hemodynamic parameters. Standard viscosity models overpredicted peak WSS by 55% and 49% for steady and pulsatile flow, respectively. Moreover, these results demonstrated non-uniform, spatial patterns of positive and negative WSS errors related to viscosity, and standard viscosity simulations overpredicted the time-averaged WSS by 32% (standard deviation = 7.1%). Finally, differences in shear rate demonstrated that the viscosity choice alters the simulated near-wall flow field, impacting hemodynamics measures. CONCLUSIONS: This work presents simulations of circle of Willis arterial flow in SCA patients and demonstrates the importance and feasibility of using a patient-specific viscosity in these simulations. Accurately characterizing cerebrovascular hemodynamics in SCA populations has potential for elucidating the pathophysiology of large-vessel occlusion, aneurysms, and tissue damage in these patients.

Capacity Building for Primary Stroke Prevention Teams in Children Living With Sickle Cell Anemia in Africa.

BACKGROUND: Nigeria has the highest proportion of children with sickle cell anemia (SCA) globally; an estimated 150,000 infants with SCA are born annually. Primary stroke prevention in children with SCA must include Nigeria. We describe capacity-building strategies in conjunction with two National Institutes of Health-funded primary stroke prevention trials (a feasibility trial and phase III randomized controlled trial) with initial hydroxyurea treatment for children with SCA and abnormal transcranial Doppler (TCD) velocities in Nigeria. We anticipated challenges to conducting clinical trials in a low-resource setting with a local team that had not previously been involved in clinical research and sought a sustainable strategy for primary stroke prevention. METHODS: This is a descriptive, prospective study of challenges, solutions, and research teams in two trials that enrolled a total of 679 children with SCA. RESULTS: As part of the capacity-building component of the trials, over eight years, 23 research personnel (physicians, nurses, research coordinators, a statistician, and a pharmacist) completed a one-month research governance and ethics training program at Vanderbilt University Medical Center, USA. A lead research coordinator for each site completed the Society of Clinical Research Professionals certification. TCD machines were donated; radiologists and nonradiologists were trained and certified to perform TCD. A scalable E-prescription was implemented to track hydroxyurea treatment. We worked with regional government officials to support ongoing TCD-based screening and funding for hydroxyurea for children with SCA at a high risk of stroke. CONCLUSIONS: Our trials and capacity building demonstrate a sustainable strategy to initiate and maintain pediatric SCA primary stroke prevention programs in Africa.

Haploidentical Allogeneic Stem Cell Transplantation in Sickle Cell Disease: A Systematic Review and Meta-Analysis.

Allogeneic hematopoietic stem cell transplantation (SCT) is the sole established curative treatment option for patients with sickle cell disease (SCD). However, a lack of HLA-identical sibling donors is a limiting factor. Haploidentical related donors are a promising donor pool, potentially extending SCT as a curative treatment option to a larger group of patients with no other meaningful treatment options for their severe SCD. In the present study, we aimed to systematically review the results of haploidentical SCT in patients with SCD. A comprehensive search was performed in MEDLINE/PubMed and Embase up to May 2021. Data were extracted by 2 reviewers independently, and the Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the studies. Fourteen studies met our inclusion criteria. To provide an overview of the results of haploidentical SCT, we grouped the studies into myeloablative conditioning versus nonmyeloablative conditioning as well as into in vitro versus in vivo (ie, with post-transplantation cyclophosphamide) T cell depletion with a subgroup meta-analysis of proportions. All the included studies were observational cohort studies. Only 3 of these studies reported data for both matched sibling donor (MSD) SCT and haploidentical SCT. Based on a comparative meta-analysis of the 3 studies that included both haploidentical and MSD transplantation, graft failure was significantly higher in the haploidentical group than in the MSD group (odds ratio, 5.3; 95% confidence interval [CI], 1.0 to 27.6). Overall survival was not significantly different between the groups. A subgroup meta-analysis of the results of haploidentical SCT showed relatively low overall pooled proportions of graft failure (7%; 95% CI, 2% to 20%), acute graft-versus-host disease (GVHD) (4%; 95% CI, 2% to 12%), and chronic GVHD (11%; 95% CI, 7% to 16%). Overall survival (OS) was high in all the included studies (91%; 95% CI, 85% to 94%). Adjustments to the conditioning regimens, robust pretransplantation and post-transplantation T cell depletion, and improved supportive care have resulted in reduced graft failure and improved OS following haploidentical SCT in patients with SCD. We conclude that the safety of haploidentical SCT in SCD patients has improved significantly, and that this should be considered as a curative option in patients with severe SCD.